ELMO2 biallelic pathogenic variants in a patient with gingival hypertrophy and cherubism phenotype: Case report and molecular review.

Ramon syndrome (OMIM #266270) was first described in a patient with cherubism, gingival fibromatosis, epilepsy, intellectual disability, hypertrichosis, and stunted growth. In 2018, Mehawej et al. described a patient with Ramon syndrome in whom a homozygous variant in ELMO2 was identified, suggesting that this gene may be the causative for this syndrome. ELMO2 biallelic pathogenic variants were also described in patients with a primary intraosseous vascular malformation (PIVM; OMIM #606893). These patients presented gingival bleeding and cherubism phenotype. Herein, a patient with gingival hypertrophy, neurodevelopmental delay, and cherubism phenotype with a novel homozygous predicted loss-of-function (LOF) variant in the ELMO2 gene and family recurrence was reported. A surgical approach to treat gingival bleeding and mandible vascular malformation was also described. Furthermore, this study includes a comprehensive literature review of molecular data regarding the ELMO2 gene. All the variants, except one described in the ELMO2, were predicted as LOF, including our patient's variant. There is an overlapping between PIVM, also caused by LOF biallelic variants in the ELMO2 gene, and Ramon syndrome, which can suggest that they are not different entities. However, due to a limited number of cases described with molecular evaluation, it is hard to establish a genotype-phenotype correlation. Our study supports that LOF pathogenic biallelic variants in the ELMO2 gene cause a phenotype that has cherubism and gingival hypertrophy as main characteristics.

Functional characterization of ligninolytic Klebsiella spp. strains associated with soil and freshwater.

Overcoming recalcitrance of lignin has motivated bioprospecting of high-yielding enzymes from environmental ligninolytic microorganisms associated with lignocellulose degrading-systems. Here, we performed isolation of 21 ligninolytic strains belonging to the genus Klebsiella spp., driven by the presence of lignin in the media. The fastest-growing strains (FP10-5.23, FP10-5.22 and P3TM1) reached the stationary phase in approximately 24 h, in the media containing lignin as the main carbon source. The strains showed biochemical evidence of ligninolytic potential in liquid- and solid media-converting dyes, which the molecular structures are similar to lignin fragments. In liquid medium, higher levels of dye decolorization was observed for P3TM.1 in the presence of methylene blue, reaching 98% decolorization in 48 h. The highest index values (1.25) were found for isolates P3TM.1 and FP10-5.23, in the presence of toluidine blue. The genomic analysis revealed the presence of more than 20 genes associated with known prokaryotic lignin-degrading systems. Identification of peroxidases (lignin peroxidase-LiP, dye-decolorizing peroxidase-DyP, manganese peroxidase-MnP) and auxiliary activities (AA2, AA3, AA6 and AA10 families) among the genetic repertoire suggest the ability to produce extracellular enzymes able to attack phenolic and non-phenolic lignin structures. Our results suggest that the Klebsiella spp. associated with fresh water and soil may play important role in the cycling of recalcitrant molecules in the Caatinga (desert-like Brazilian biome), and represent a potential source of lignin-degrading enzymes with biotechnological applications.

Diversity of Microbial Carbohydrate-Active enZYmes (CAZYmes) Associated with Freshwater and Soil Samples from Caatinga Biome.

Semi-arid and arid areas occupy about 33% of terrestrial ecosystems. However, little information is available about microbial diversity in the semi-arid Caatinga, which represents a unique biome that extends to about 11% of the Brazilian territory and is home to extraordinary diversity and high endemism level of species. In this study, we characterized the diversity of microbial genes associated with biomass conversion (carbohydrate-active enzymes, or so-called CAZYmes) in soil and freshwater of the Caatinga. Our results showed distinct CAZYme profiles in the soil and freshwater samples. Glycoside hydrolases and glycosyltransferases were the most abundant CAZYme families, with glycoside hydrolases more dominant in soil (∼44%) and glycosyltransferases more abundant in freshwater (∼50%). The abundances of individual glycoside hydrolase, glycosyltransferase, and carbohydrate-binding module subfamilies varied widely between soil and water samples. A predominance of glycoside hydrolases was observed in soil, and a higher contribution of enzymes involved in carbohydrate biosynthesis was observed in freshwater. The main taxa associated with the CAZYme sequences were Planctomycetia (relative abundance in soil, 29%) and Alphaproteobacteria (relative abundance in freshwater, 27%). Approximately 5-7% of CAZYme sequences showed low similarity with sequences deposited in non-redundant databases, suggesting putative homologues. Our findings represent a first attempt to describe specific microbial CAZYme profiles for environmental samples. Characterizing these enzyme groups associated with the conversion of carbohydrates in nature will improve our understanding of the significant roles of enzymes in the carbon cycle. We identified a CAZYme signature that can be used to discriminate between soil and freshwater samples, and this signature may be related to the microbial species adapted to the habitat. The data show the potential ecological roles of the CAZYme repertoire and associated biotechnological applications.